What is Monoclonal Gammopathy of Undetermined Significance (MGUS)?

From the Guidelines

Patients with MGUS should be followed with serum protein electrophoresis at six months and, if stable, can be followed every 2–3 years or when symptoms suggestive of a plasma cell malignancy arise. MGUS, or Monoclonal Gammopathy of Undetermined Significance, is a precancerous condition characterized by the presence of an abnormal protein (M protein) in the blood produced by plasma cells. This condition requires regular monitoring but typically doesn't need treatment unless it progresses.

Key Considerations

• The risk of progression to multiple myeloma or related malignancy is approximately 1% per year 1.
• Risk factors for progression include higher M protein levels, non-IgG type M protein, abnormal free light chain ratio, and abnormal bone marrow plasma cell percentage.
• Low-risk MGUS is characterized by having an M protein <15 g/l, IgG type and a normal free light chain (FLC) ratio 1.
• Patients with low-risk MGUS do not require a baseline BM examination or skeletal radiography if the clinical evaluation, complete blood count, serum creatinine and calcium values suggest MGUS 1.

Monitoring and Management

• Patients should be informed about symptoms that might indicate progression, such as bone pain, unexplained fatigue, recurrent infections, or kidney problems.
• Testing should be done 2–3 months after the initial recognition of MGUS, and if the results are stable, the patient should be followed every 4–6 months for 1 year and, if stable, every 6–12 months 1.
• MGUS is relatively common, affecting about 3% of people over age 50, and results from genetic changes in plasma cells that cause them to produce abnormal proteins without forming a cancerous mass 1.

From the Research

Definition and Diagnosis of MGUS

• Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant plasma cell dyscrasia that consistently precedes multiple myeloma (MM) with a 1% risk of progression per year 2
• MGUS is defined by the absence of end-organ damage or symptoms, a small amount of monoclonal immunoglobulin (M protein), and low volume of plasma cells 3
• The diagnosis of MGUS is often made incidentally during the evaluation of other clinical concerns, and the top indications for prediagnostic testing include neuropathy, renal disease, anemia, bone disorder or connective tissue pain, and cutaneous disease 4

Risk of Progression and Management

• The risk of progression from MGUS to multiple myeloma ranges from 0.5% to 1.0% per year 3, 5
• Patients with MGUS can be risk-stratified on the basis of the amount and type of their monoclonal protein as well as whether they have an abnormal light-chain ratio 6
• Guideline-concordant management of MGUS is determined by predicted risk of progression to malignant disease, which depends on subtype of immunoglobulin, M protein concentration, and free light chain ratio 3
• Patients with low-risk MGUS can safely defer bone marrow biopsy and advanced imaging, and should undergo periodic laboratory monitoring, while intermediate- and high-risk MGUS should trigger bone marrow biopsy and bone imaging to detect overt MM and shorter monitoring intervals 3

Clinical Follow-up and Survival

• Prior knowledge of MGUS among multiple myeloma patients is associated with significantly better overall survival, suggesting that earlier treatment of MM leads to better survival 5
• Patients with MGUS should have regular clinical follow-up, regardless of risk stratification, and the intensity of follow-up should be based on risk factors and clinical practice guidelines 4
• Hematologists are more likely to follow patients with MGUS more closely than nonhematologists, but the variation in follow-up practice is not based on risk factors or clinical practice guidelines 4